Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo

Eunju Leem; Hyung Jun Kim; Minji Choi; Sehwan Kim; Yong Seok Oh; Kea Joo Lee; Young Shik Choe; Jae Young Um; Won Ho Shin; Jae Yeong Jeong; Byung Kwan Jin; Dong Woon Kim; Catriona McLean; Paul B. Fisher; Nikolai Kholodilov; Kwang Seok Ahn; Jae Man Lee; Un Ju Jung; Seok Geun Lee; Sang Ryong Kim

doi:10.1038/s41419-018-0491-3

Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo

Eunju Leem, Hyung Jun Kim, Minji Choi, Sehwan Kim, Yong Seok Oh, Kea Joo Lee, Young Shik Choe, Jae Young Um, Won Ho Shin, Jae Yeong Jeong, Byung Kwan Jin, Dong Woon Kim, Catriona McLean, Paul B. Fisher, Nikolai Kholodilov, Kwang Seok Ahn, Jae Man Lee, Un Ju Jung, Seok Geun Lee, Sang Ryong Kim

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Abstract

The role of astrocyte elevated gene-1 (AEG-1) in nigral dopaminergic (DA) neurons has not been studied. Here we report that the expression of AEG-1 was significantly lower in DA neurons in the postmortem substantia nigra of patients with Parkinson's disease (PD) compared to age-matched controls. Similarly, decreased AEG-1 levels were found in the 6-hydroxydopamine (6-OHDA) mouse model of PD. An adeno-associated virus-induced increase in the expression of AEG-1 attenuated the 6-OHDA-triggered apoptotic death of nigral DA neurons. Moreover, the neuroprotection conferred by the AEG-1 upregulation significantly intensified the neurorestorative effects of the constitutively active ras homolog enriched in the brain [Rheb(S16H)]. Collectively, these results demonstrated that the sustained level of AEG-1 as an important anti-apoptotic factor in nigral DA neurons might potentiate the therapeutic effects of treatments, such as Rheb(S16H) administration, on the degeneration of the DA pathway that characterizes PD.

Original language	English
Article number	449
Journal	Cell Death and Disease
Volume	9
Issue number	5
DOIs	https://doi.org/10.1038/s41419-018-0491-3
State	Published - 1 Jan 2018

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Leem, E., Kim, H. J., Choi, M., Kim, S., Oh, Y. S., Lee, K. J., Choe, Y. S., Um, J. Y., Shin, W. H., Jeong, J. Y., Jin, B. K., Kim, D. W., McLean, C., Fisher, P. B., Kholodilov, N., Ahn, K. S., Lee, J. M., Jung, U. J., Lee, S. G., & Kim, S. R. (2018). Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo. Cell Death and Disease, 9(5), Article 449. https://doi.org/10.1038/s41419-018-0491-3

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title = "Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo",

abstract = "The role of astrocyte elevated gene-1 (AEG-1) in nigral dopaminergic (DA) neurons has not been studied. Here we report that the expression of AEG-1 was significantly lower in DA neurons in the postmortem substantia nigra of patients with Parkinson's disease (PD) compared to age-matched controls. Similarly, decreased AEG-1 levels were found in the 6-hydroxydopamine (6-OHDA) mouse model of PD. An adeno-associated virus-induced increase in the expression of AEG-1 attenuated the 6-OHDA-triggered apoptotic death of nigral DA neurons. Moreover, the neuroprotection conferred by the AEG-1 upregulation significantly intensified the neurorestorative effects of the constitutively active ras homolog enriched in the brain [Rheb(S16H)]. Collectively, these results demonstrated that the sustained level of AEG-1 as an important anti-apoptotic factor in nigral DA neurons might potentiate the therapeutic effects of treatments, such as Rheb(S16H) administration, on the degeneration of the DA pathway that characterizes PD.",

author = "Eunju Leem and Kim, {Hyung Jun} and Minji Choi and Sehwan Kim and Oh, {Yong Seok} and Lee, {Kea Joo} and Choe, {Young Shik} and Um, {Jae Young} and Shin, {Won Ho} and Jeong, {Jae Yeong} and Jin, {Byung Kwan} and Kim, {Dong Woon} and Catriona McLean and Fisher, {Paul B.} and Nikolai Kholodilov and Ahn, {Kwang Seok} and Lee, {Jae Man} and Jung, {Un Ju} and Lee, {Seok Geun} and Kim, {Sang Ryong}",

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year = "2018",

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doi = "10.1038/s41419-018-0491-3",

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Leem, E, Kim, HJ, Choi, M, Kim, S, Oh, YS, Lee, KJ, Choe, YS, Um, JY, Shin, WH, Jeong, JY, Jin, BK, Kim, DW, McLean, C, Fisher, PB, Kholodilov, N, Ahn, KS, Lee, JM, Jung, UJ, Lee, SG & Kim, SR 2018, 'Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo', Cell Death and Disease, vol. 9, no. 5, 449. https://doi.org/10.1038/s41419-018-0491-3

TY - JOUR

T1 - Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo

AU - Leem, Eunju

AU - Kim, Hyung Jun

AU - Choi, Minji

AU - Kim, Sehwan

AU - Oh, Yong Seok

AU - Lee, Kea Joo

AU - Choe, Young Shik

AU - Um, Jae Young

AU - Shin, Won Ho

AU - Jeong, Jae Yeong

AU - Jin, Byung Kwan

AU - Kim, Dong Woon

AU - McLean, Catriona

AU - Fisher, Paul B.

AU - Kholodilov, Nikolai

AU - Ahn, Kwang Seok

AU - Lee, Jae Man

AU - Jung, Un Ju

AU - Lee, Seok Geun

AU - Kim, Sang Ryong

PY - 2018/1/1

Y1 - 2018/1/1

N2 - The role of astrocyte elevated gene-1 (AEG-1) in nigral dopaminergic (DA) neurons has not been studied. Here we report that the expression of AEG-1 was significantly lower in DA neurons in the postmortem substantia nigra of patients with Parkinson's disease (PD) compared to age-matched controls. Similarly, decreased AEG-1 levels were found in the 6-hydroxydopamine (6-OHDA) mouse model of PD. An adeno-associated virus-induced increase in the expression of AEG-1 attenuated the 6-OHDA-triggered apoptotic death of nigral DA neurons. Moreover, the neuroprotection conferred by the AEG-1 upregulation significantly intensified the neurorestorative effects of the constitutively active ras homolog enriched in the brain [Rheb(S16H)]. Collectively, these results demonstrated that the sustained level of AEG-1 as an important anti-apoptotic factor in nigral DA neurons might potentiate the therapeutic effects of treatments, such as Rheb(S16H) administration, on the degeneration of the DA pathway that characterizes PD.

AB - The role of astrocyte elevated gene-1 (AEG-1) in nigral dopaminergic (DA) neurons has not been studied. Here we report that the expression of AEG-1 was significantly lower in DA neurons in the postmortem substantia nigra of patients with Parkinson's disease (PD) compared to age-matched controls. Similarly, decreased AEG-1 levels were found in the 6-hydroxydopamine (6-OHDA) mouse model of PD. An adeno-associated virus-induced increase in the expression of AEG-1 attenuated the 6-OHDA-triggered apoptotic death of nigral DA neurons. Moreover, the neuroprotection conferred by the AEG-1 upregulation significantly intensified the neurorestorative effects of the constitutively active ras homolog enriched in the brain [Rheb(S16H)]. Collectively, these results demonstrated that the sustained level of AEG-1 as an important anti-apoptotic factor in nigral DA neurons might potentiate the therapeutic effects of treatments, such as Rheb(S16H) administration, on the degeneration of the DA pathway that characterizes PD.

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DO - 10.1038/s41419-018-0491-3

M3 - Article

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AN - SCOPUS:85045767128

SN - 2041-4889

VL - 9

JO - Cell Death and Disease

JF - Cell Death and Disease

IS - 5

M1 - 449

ER -

Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo

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